Clinical, pathological and molecular genetic analysis of pediatric lipid storage myopathy

Abstract

Objective To analyze the clinical, pathological and molecular genetic data from 15 children with pathologically demonstrated lipid storage myopathy(LSM), and to explore the spectrum of causes, establish approaches on diagnosis and treatment of LSM in children. Methods Clinical data were retrospectively analyzed, including medical history, muscle pathology, urine amino acids and organic acids analysis, blood amino acids and acylcarnitine spectrum analysis.SLC22A5 and PNPLA2 gene mutations were detected.The follow-ups lasted from 5 months to 5 years and 4 months. Results Out of 15 cases, the onset of the disease was occult in 13 patients, subacute in 2 patients.Muscle weakness and exercise intolerance were presented in 13 patients, while 2 patients were asymptomatic with elevated serum creatine kinase levels.Muscle pathology in all patients showed accumulation of lipid drops in skeletal muscle fibers.Glutaric aciduria type Ⅱ was diagnosed in 5 cases by urinary and blood metabolic screening while no specific changes were found in 10 cases.SLC22A5 and PNPLA2 genes mutational analysis by PCR and sequencing were performed in these 10 cases, and no causative mutations were found.Thirteen patients were treated with vitamin B2, carnitine and coenzyme Q10, 5 patients with glutaric aciduria type Ⅱ regained normal exercise capacity; 7 cases out of 8 cases with unknown causes had improvement of muscle strength and exercise tolerance, 1 case died.Two patients who refused drug treatment still present with exercise intolerance. Conclusions The causes of lipid storage myopathy were variant.Combined laboratory tests including blood acylcarnitine spectrum analysis, urine organic acids analysis, and genetic testing, may confirm the causes of some patients.Glutaric aciduria type Ⅱ may be the most common cause of LSM in Chinese children.Although the responses to treatment depend mainly on the causes, L-carnitine, Vitamin B2 and CoQ10 may improve the clinical symptoms in most patients. Key words: Lipid storage myopathy; Muscle biopsy; Urine organic analysis; Blood acylcarnitine spectrum analysis; Genetic testing